Short Report: Beneficial Effects of Benznidazole during an Infectious-based Situation of Systemic Inflammatory Response: Cecal Ligation and Puncture

Abstract. We have shown that benznidazole (BZL), a drug used to treat Chagas disease, markedly reduced the production of pro-inflammatory cytokines and NO-derived metabolites in experimentally Trypanosoma cruzi–infected rats. Treatment with BZL exerted beneficial effects in a model of inflammation-based pathology like murine experi-mental endotoxemia. Based on these findings, we wished to ascertain the effect of BZL in a closer situation to sepsis: the cecal ligation and puncture (CLP) model in C57BL/6 mice. We analyzed clinical course, survival, circulating levels of inflammation-related compounds (NO, tumor necrosis factor [TNF]-), and bacteriemia. Recipients of BZL, 25 mg/kg, had an increased survival rate at 24 hours after CLP, showing a better clinical situation and a significant reduction of TNF- levels and bacteriemia, with respect to the other groups. BZL failed to inhibit in vitro bacterial growth, suggesting that these effects may be partly caused by the immunomodulatory effects of BZL. Benznidazole (BZL) has been used for the treatment of acute Chagas ’ disease for more than three decades. In addi-tion to its trypanocidal activity, our studies indicate that BZL also affects the synthesis of important biological response modifiers with potential implications in inflammatory pro-cesses. By using different experimental approaches, it wa